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Human embryonic stem cell‐derived neural precursors as a continuous, stable, and on‐demand source for human dopamine neurons
Author(s) -
Ko JiYun,
Park ChangHwan,
Koh HyunChul,
Cho YoulHee,
Kyhm JeeHong,
Kim YoungSoo,
Lee Inchul,
Lee YongSung,
Lee SangHun
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04898.x
Subject(s) - embryonic stem cell , biology , microbiology and biotechnology , transplantation , stem cell , cellular differentiation , dopamine , in vitro , neural stem cell , phenotype , striatum , cell , cell culture , neuroscience , medicine , gene , biochemistry , genetics
Human embryonic stem (hES) cells can be guided to differentiate into ventral midbrain‐type neural precursor (NP) cells that proliferate in vitro by specific mitogens. We investigated the potential of these NP cells derived from hES cells (hES‐NP) for the large‐scale generation of human dopamine (DA) neurons for functional analyses and therapeutic applications. To address this, hES‐NP cells were expanded in vitro for 1.5 months with six passages, and their proliferation and differentiation properties determined over the NP passages. Interestingly, the total hES‐NP cell number was increased by > 2 × 10 4 ‐folds over the in vitro period without alteration of phenotypic gene expression. They also sustained their differentiation capacity toward neuronal cells, exhibiting in vitro pre‐synaptic DA neuronal functionality. Furthermore, the hES‐NP cells can be cryopreserved without losing their proliferative and developmental potential. Upon transplantation into a Parkinson’s disease rat model, the multi‐passaged hES‐NP cells survived, integrated into the host striatum, and differentiated toward the neuronal cells expressing DA phenotypes. A significant reduction in the amphetamine‐induced rotation score of Parkinson’s disease rats was observed by the cell transplantation. Taken together, these findings indicate that hES‐NP cell expansion is exploitable for a large‐scale generation of experimental and transplantable DA neurons of human‐origin.